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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (6)

ORF1 (1)

ORF3a (1)

ProteinN (1)

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    Allelic variation in Class I HLA determines pre-existing memory responses to SARS-CoV-2 that shape the CD8 HGNC+ T cell repertoire upon viral exposure

    Authors: Joshua M Francis; Del Leistritz-Edwards; Augustine Dunn; Christina Tarr; Jesse Lehman; Conor Dempsey; Andrew Hamel; Violeta Rayon; Gang Liu; Yuntong Wang; Marcos Wille; Melissa Durkin; Kane Hadley; Aswathy Sheen; Benjamin Roscoe; Mark Ng; Graham Rockwell; Margaret Manto; Elizabeth Gienger; Joshua Nickerson; - MGH COVID-19 Collection and Processing Team; Amir Moarefi; Michael Noble; Thomas Malia; Philip D Bardwell; William Gordon; Joanna Swain; Mojca Skoberne; Karsten Sauer; Tim Harris; Ananda W Goldrath; Alex K Shalek; Anthony J Coyle; Christophe Benoist; Daniel C Pregibon

    doi:10.1101/2021.04.29.441258 Date: 2021-04-29 Source: bioRxiv

    Effective presentation of antigens by HLA class I molecules to CD8 HGNC+ T cells is required for viral elimination and generation of long-term immunological memory. In this study, we applied a single-cell, multi-omic technology to generate the first unified ex vivo characterization of the CD8 HGNC+ T cell response to SARS-CoV-2 across 4 major HLA class I alleles. We found that HLA genotype conditions key features of epitope specificity, TCR HGNC a/b sequence diversity, and the utilization of pre-existing SARS-CoV-2 reactive memory T MESHD cell pools. Single-cell transcriptomics revealed functionally diverse T cell phenotypes of SARS-CoV-2-reactive T cells, associated with both disease stage and epitope specificity. Our results show that HLA variations influence pre-existing immunity to SARS-CoV-2 and shape the immune repertoire upon subsequent viral exposure.

    Strong anti-viral responses in pediatric COVID-19 MESHD patients in South Brazil

    Authors: Tiago Fazolo; Karina Lima; Julia C. Fontoura; Priscila Oliveira de Souza; Gabriel Hilario; Renata Zorzetto; Luiz Rodrigues Jr.; Veridiane Maria Pscheidt; Jayme Ferreira Neto; Alisson F. Haubert; Izza Gambin; Aline C. Oliveira; Raissa S. Mello; Matheus Gutierrez; Rodrigo Benedetti Gassen; Ivaine Tais Sauthier Sartor; Gabriela Oliveira Zavaglia; Ingrid Rodrigues Fernandes; Fernanda Hammes Varela; Márcia Polese-Bonatto; Thiago J. Borges; Sidia Maria Callegari-Jacques; Marcela Santos Correa da Costa; Jaqueline de Araujo Schwartz; Marcelo Comerlato Scotta; Renato T. Stein; Cristina Bonorino

    doi:10.1101/2021.04.13.21255139 Date: 2021-04-16 Source: medRxiv

    Epidemiological evidence that COVID-19 MESHD manifests as a milder disease in children compared to adults has been reported by numerous studies, but the mechanisms underlying this phenomenon have not been characterized. It is still unclear how frequently children get infected, and/or generate immune responses to SARS-CoV-2. We have performed immune profiling of pediatric and adult COVID-19 MESHD patients in Brazil, producing over 38 thousand data points, asking if cellular or humoral immune responses could help explain milder disease in children. In this study, pediatric COVID-19 MESHD patients presented high viral titers. Though their non-specific immune profile was dominated by naive, non-activated lymphocytes, their dendritic cells expressed high levels of HLA-DR and were low in CX3CR1 HGNC, indicating competence to generate immune responses that are not targeted to inflamed tissue. Finally, children formed strong specific antibody and T cell responses for viral structural proteins. Children s T cell responses differed from adults in that their CD8 HGNC+ TNF+ T cell responses were low for S peptide but significantly higher against N and M peptide pools. Altogether, our data support a scenario in which SARS-CoV-2 infected MESHD children may contribute to transmission, though generating strong and differential responses to the virus that might associate with protection in pediatric COVID-19 MESHD presentation.

    IL-15 HGNC and sMAdCAM: Novel roles in COVID-19 MESHD pathogenesis

    Authors: Amit Kumar Singh; Nandini Jayant Kasarpalkar; Shilpa Dinesh Kumar Bhowmick; Gaurav Paradkar; Mayur Talreja; Karan Shah; Abhishek Tiwari; Harsha Chandrashekhar Palav; Snehal Nagendra Kaginkar; Rajiv Kulkarni; Ashwini Patil; Varsha Kalsurkar; Sachee Agrawal; Jayanthi Shastri; Rajesh Dere; Ramesh Bharmal; Smita D Mahale; Vikrant M Bhor; Vainav Patel

    doi:10.1101/2021.03.25.21254215 Date: 2021-03-29 Source: medRxiv

    Immune cell dysregulation and lymphopenia MESHD characterize COVID-19 MESHD pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study we evaluated the association of circulating IL-6 HGNC, soluble mucosal addressin cell adhesion molecule (sMAdCAM) and IL-15 HGNC with cellular dysfunction characterizing mild and hypoxemic stages of COVID-19 MESHD. A cohort of SARS-CoV-2 infected MESHD individuals (n=125) at various stages of disease progression together with healthy controls (n=16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in-depth immune subset characterization and to measure plasma IL-6 HGNC levels. sMAdCAM, IL-15 HGNC levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 HGNC effector memory and CD4 HGNC+ regulatory T cells was observed in hypoxemic disease MESHD within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease MESHD. IL-6 HGNC levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho-depletion suggesting opposing roles in pathogenesis. Interestingly, IL-15 HGNC, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, negative association of plasma IL-15 HGNC with depleted T, B and NK subsets suggested a compensatory production of this cytokine in response to the profound lymphopenia MESHD. Finally, higher levels of plasma IL-15 HGNC and IL-6 HGNC, but not sMAdCAM, were associated with longer duration of hospitalization.

    A new concept on anti-SARS-CoV-2 vaccines: strong CD8 HGNC+ T-cell immune response in both spleen and lung induced in mice by endogenously engineered extracellular vesicles

    Authors: Flavia Ferrantelli; Chiara Chiozzini; Francesco Manfredi; Patrizia Leone; Maurizio Federico

    doi:10.1101/2020.12.18.423420 Date: 2020-12-18 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 MESHD is spreading rapidly in the absence of validated tools to control the growing epidemic besides social distancing and masks. Many efforts are ongoing for the development of vaccines against SARS-CoV-2 since there is an imminent need to develop effective interventions for controlling and preventing SARS-CoV-2 spread. Essentially all vaccines in most advanced phases are based on the induction of antibody response against either whole or part of spike (S) protein PROTEIN. Differently, we developed an original strategy to induce CD8 HGNC+ T cytotoxic lymphocyte (CTL) immunity based on in vivo engineering of extracellular vesicles (EVs). We exploited this technology with the aim to identify a clinical candidate defined as DNA vectors expressing SARS-CoV-2 antigens inducing a robust CD8 HGNC+ T-cell response. This is a new vaccination approach employing a DNA expression vector encoding a biologically inactive HIV-1 Nef protein (Nefmut) showing an unusually high efficiency of incorporation into EVs even when foreign polypeptides are fused to its C-terminus. Nanovesicles containing Nefmut-fused antigens released by muscle cells are internalized by antigen-presenting cells leading to cross-presentation of the associated antigens thereby priming of antigen-specific CD8 HGNC+ T-cells. To apply this technology to a design of anti-SARS-CoV-2 vaccine, we recovered DNA vectors expressing the products of fusion between Nefmut and four viral antigens, namely N- and C-terminal moieties of S (referred to as S1 and S2), M, and N. All fusion products are efficiently uploaded in EVs. When the respective DNA vectors were injected in mice, a strong antigen-specific CD8 HGNC+ T cell immunity was generated. Most important, high levels of virus-specific CD8 HGNC+ T cells were found in bronchoalveolar lavages of immunized mice. Co-injection of DNA vectors expressing the diverse SARS-CoV-2 antigens resulted in additive immune responses in both spleen and lung. EVs engineered with SARS-CoV-2 antigens proved immunogenic also in the human system through cross-priming assays carried out with ex vivo human cells. Hence, DNA vectors expressing Nefmut-based fusion proteins can be proposed as anti-SARS-CoV-2 vaccine candidates.

    BCG vaccine derived peptides induce SARS-CoV-2 T cell cross-reactivity

    Authors: Peter J Eggenhuizen; Boaz H Ng; Janet Chang; Ashleigh L Fell; Wey Y Wong; Poh-yi Gan; Stephen R Holdsworth; Joshua D Ooi

    doi:10.1101/2020.11.21.20236018 Date: 2020-11-23 Source: medRxiv

    Epidemiological studies suggest that the Bacillus Calmette-Guerin (BCG) vaccine may have protective effects against coronavirus disease 2019 MESHD ( COVID-19 MESHD); and, there are now more than 15 ongoing clinical trials seeking to determine if BCG vaccination can prevent or reduce the severity of COVID-19 MESHD (1). However, the mechanism by which BCG vaccination can induce a severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) specific T cell response is unknown. Here, in silico, we identify 8 BCG derived peptides with significant sequence homology to either SARS-CoV-2 NSP3 MESHD NSP3 PROTEIN NSP3 HGNC or NSP13 PROTEIN derived peptides. Using an in vitro co-culture system, we show that human CD4 HGNC+ and CD8 HGNC+ T cells primed with a BCG derived peptide developed enhanced reactivity to its corresponding SARS-CoV-2 derived peptide. As expected, HLA differences between individuals meant that not all persons developed immunogenic responses to all 8 BCG derived peptides. Nevertheless, all of the 20 individuals that were primed with BCG derived peptides developed enhanced T cell reactivity to at least 7 of 8 SARS-CoV-2 derived peptides. These findings provide a mechanistic basis for the epidemiologic observation that BCG vaccination confers protection from COVID-19 MESHD; and supports the use of BCG vaccination to induce cross-reactive SARS-CoV-2 specific T cell responses.

    SARS-CoV-2-specific T cell memory is long-lasting in the majority of convalsecent COVID-19 MESHD individuals

    Authors: Ziwei Li; Jing Liu; Hui Deng; Xuecheng Yang; Hua Wang; Xuemei Feng; Gennadiy Zelinskyy; Mirko Trilling; Kathrin Sutter; Mengji Lu; Baoju Wang; Dongliang Yang; Xin Zheng; Jia Liu; Davey Smith; Daniela Weiskopf; Alessandro Sette; Shane Crotty; Jian Jin; Xian Chen; Andrew Pekosz; Sabra Klein; Irina Burd

    doi:10.1101/2020.11.15.383463 Date: 2020-11-16 Source: bioRxiv

    An unaddressed key question in the current coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic is the duration of immunity for which specific T cell responses against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an indispensable element. Being situated in Wuhan where the pandemic initiated enables us to conduct the longest analyses of memory T MESHD cell responses against SARS-CoV-2 in COVID-19 MESHD convalescent individuals (CIs). Magnitude and breadth of SARS-CoV-2 memory MESHD CD4 HGNC and CD8 HGNC T cell responses were heterogeneous between patients but robust responses could be detected up to 9 months post disease onset in most CIs. Loss of memory CD4 HGNC and CD8 HGNC T cell responses were observed in only 16.13% and 25.81% of CIs, respectively. Thus, the overall magnitude and breadth of memory CD4 HGNC and CD8 HGNC T cell responses were quite stable and not inversely correlated with the time from disease onset. Interestingly, the only significant decrease in the response was found for memory CD4 HGNC T cells in the first 6-month post COVID-19 MESHD disease onset. Longitudinal analyses revealed that the kinetics of SARS-CoV-2 memory MESHD CD4 HGNC and CD8 HGNC T cell responses were quite heterogenous between patients. Loss of memory CD4 T MESHD CD4 HGNC T cell responses was observed more frequently in asymptomatic cases than after symptomatic COVID-19 MESHD. Interestingly, the few CIs in which SARS-CoV-2-specific IgG responses disappeared showed more durable memory CD4 HGNC T cell responses than CIs who remained IgG-positive for month. Collectively, we provide the first comprehensive characterization of the long-term memory T cell response in CIs, suggesting that SARS-CoV-2-specific T cell immunity is long-lasting in the majority of individuals.

    Mapping the recovery of critically ill COVID19 MESHD patients by high-dimensional profiling identifies longitudinal blood immunotypes

    Authors: Penttilä PA; Van Gassen S; Panovska D; Vanderbeke L; Van Herck Y; Quintelier K; Emmaneel A; Filtjens J; Malengier-Devlies B; Ahmadzadeh K; Van Mol P; Borras DM; Antoranz A; Bosisio F; Wauters E.; Matthys P; Saeys Y; Garg A; Wauters J; De Smet F

    doi:10.21203/rs.3.rs-108268/v1 Date: 2020-11-13 Source: ResearchSquare

    The COVID-19 MESHD COVID-19 MESHD pandemic poses a major burden on health-care and economic systems across the globe. Even though a majority of the population only develops minor symptoms upon SARS-CoV2 infection MESHD, a significant proportion are hospitalized at intensive care units (ICU) requiring critical care. While insights into the early stages of the disease are gradually expanding, the dynamic immunological processes occurring in critically ill MESHD patients throughout their recovery at ICU are far less understood. Here, we have analysed longitudinally collected, whole blood samples of 40 surviving COVID-19 MESHD patients during their recovery at ICU using high-dimensional cytometry by time-of-flight (CyTOF) and cytokine multiplexing. Based on the neutrophil to lymphocyte ratio (NLR), we defined 4 sequential immunotypes during recovery that correlated to various clinical parameters, including the level of respiratory support at concomitant sampling times. We also identified classical monocytes as the first immune cell type to recover by restoring HLA-DR-positivity and by reducing the immunosuppressive CD163+ monocyte population, followed by the recovery of CD8 HGNC+ and CD4 HGNC+ T cell, and mDC populations. The identified immunotypes also correlated to aberrant cytokine and acute-phase reactant levels. Finally, integrative analysis of cytokines and immune cell profiles showed a shift from an initially dysregulated immune response to a more coordinated immunogenic interplay, highlighting the importance of longitudinal sampling to understand the pathophysiology underlying recovery from severe COVID-19 MESHD.

    Broad SARS-CoV-2 cell tropism and immunopathology in lung tissues from fatal COVID-19 MESHD

    Authors: Suzane Ramos da Silva; Enguo Ju; Wen Meng; Alberto E. Paniz Mondolfi; Sanja Dacic; Anthony Green; Clare Bryce; Zachary Grimes; Mary E Fowkes; Emilia M. Sordillo; Carlos Cordon-Cardo; Haitao Guo; Shou-Jiang Gao

    doi:10.1101/2020.09.25.20195818 Date: 2020-09-29 Source: medRxiv

    Background Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection MESHD in patients with Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) prominently manifests with pulmonary symptoms histologically reflected by diffuse alveolar damage MESHD (DAD), excess inflammation MESHD, pneumocyte hyperplasia MESHD and proliferation, and formation of platelet aggregates or thromboemboli MESHD. However, the mechanisms mediating these processes remain unclear. Methods We performed multicolor staining for viral proteins, and lineage cell markers to identify SARS-CoV-2 tropism MESHD and to define the lung pathobiology in postmortem tissues from five patients with fatal SARS-CoV-2 infections MESHD SARS-CoV-2 infections MESHD. Findings The lung parenchyma showed severe DAD MESHD with thromboemboli MESHD in all cases. SARS-CoV-2 infection MESHD was found in an extensive range of cells including alveolar epithelial type II/pneumocyte type II MESHD (AT2) cells (HT2-280), ciliated cells (tyr--tubulin), goblet cells ( MUC5AC HGNC), club-like cells ( MUC5B HGNC) and endothelial cells ( CD31 HGNC and CD34 HGNC). Greater than 90% of infiltrating immune cells were positive for viral proteins including macrophages and monocytes ( CD68 HGNC and CD163 HGNC), neutrophils ( ELA-2 HGNC), natural killer (NK) cells ( CD56 HGNC), B-cells ( CD19 HGNC and CD20 HGNC), and T-cells (CD3{varepsilon}). Most but not all infected cells were positive for the viral entry receptor angiotensin-converting enzyme-2 HGNC ( ACE2 HGNC). The numbers of infected and ACE2 HGNC-positive cells correlated with the extent of tissue damage. The infected tissues exhibited low numbers of B-cells and abundant CD3{varepsilon}+ T-cells consisting of mainly T helper cells ( CD4 HGNC), few cytotoxic T cells (CTL, CD8 HGNC), and no T regulatory cell ( FOXP3 HGNC). Antigen presenting molecule HLA-DR of B and T cells was abundant in all cases. Robust interleukin-6 HGNC ( IL-6 HGNC) expression was present in most uninfected and infected cells, with higher expression levels observed in cases with more tissue damage. Interpretation In lung tissues from severely affected COVID-19 MESHD patients, there is evidence for broad SARS-CoV-2 cell tropisms, activation of immune cells, and clearance of immunosuppressive cells, which could contribute to severe tissue damage, thromboemboli, excess inflammation MESHD and compromised adaptive immune responses.

    Genome-Wide Asymptomatic B-Cell, CD4 HGNC+ and CD8 HGNC+ T-Cell Epitopes, that are Highly Conserved Between Human and Animal Coronaviruses, Identified from SARS-CoV-2 as Immune Targets for Pre-Emptive Pan-Coronavirus Vaccines

    Authors: Swayam Prakash; Srivastava Ruchi; Pierre-Gregoire Coulon; Nisha R Dhanushkodi; Aziz A Chentoufi; Delia F Tifrea; Robert A Edwards; Cesar J Figueroa; Sebastian D Schubl; Lanny, Hsieh; Michael J Buchmeier; Mohammed Bouziane; Anthony B Nesburn; Baruch D Kuppermann; Lbachir BenMohamed; Volkher Scharnhorst; Heidi Ammerlaan; Kathleen Deiteren; Stephan J.L. Bakker; Lucas Joost van Pelt; Yvette Kluiters-de Hingh; Mathie P.G. Leers; Andre van der Ven; Luciana C. Ribeiro; Marcus V. Agrela; Maria Luiza Moretti; Lucas I. Buscaratti; Fernanda Crunfli; Raissa . G Ludwig; Jaqueline A. Gerhardt; Renata Seste-Costa; Julia Forato; Mariene . R Amorin; Daniel A. T. Texeira; Pierina L. Parise; Matheus C. Martini; Karina Bispo-dos-Santos; Camila L. Simeoni; Fabiana Granja; Virginia C. Silvestrini; Eduardo B. de Oliveira; Vitor M. Faca; Murilo Carvalho; Bianca G. Castelucci; Alexandre B. Pereira; Lais D. Coimbra; Patricia B. Rodrigues; Arilson Bernardo S. P. Gomes; Fabricio B. Pereira; Leonilda M. B. Santos; Andrei C. Sposito; Robson F. Carvalho; Andre S. Vieira; Marco A. R. Vinolo; Andre Damasio; Licio A. Velloso; Helder I. Nakaya; Henrique Marques-Souza; Rafael E. Marques; Daniel Martins-de-Souza; Munir S. Skaf; Jose Luiz Proenca-Modena; Pedro M. Moraes-Vieira; Marcelo A. Mori; Alessandro S. Farias

    doi:10.1101/2020.09.27.316018 Date: 2020-09-28 Source: bioRxiv

    Over the last two decades, there have been three deadly human outbreaks of Coronaviruses (CoVs) caused by emerging zoonotic CoVs: SARS-CoV MESHD, MERS-CoV, and the latest highly transmissible and deadly SARS-CoV-2 MESHD, which has caused the current COVID-19 MESHD global pandemic. All three deadly CoVs originated from bats, the natural hosts, and transmitted to humans via various intermediate animal reservoirs. Because there is currently no universal pan-Coronavirus vaccine available, two worst-case scenarios remain highly possible: (1) SARS-CoV-2 mutates and transforms into a seasonal flu-like global pandemic; and/or (2) Other global COVID-like pandemics will emerge in the coming years, caused by yet another spillover of an unknown zoonotic bat-derived SARS-like Coronavirus (SL-CoV) into an unvaccinated human population. Determining the antigen and epitope landscapes that are conserved among human and animal Coronaviruses as well as the repertoire, phenotype and function of B cells and CD4 HGNC+ and CD8 HGNC+ T cells that correlate with resistance seen in asymptomatic COVID-19 MESHD patients should inform in the development of pan-Coronavirus vaccines. In the present study, using several immuno-informatics and sequence alignment approaches, we identified several human B-cell, CD4 HGNC+ and CD8 HGNC+ T cell epitopes that are highly conserved in: (i) greater than 81,000 SARS-CoV-2 human strains identified to date in 190 countries on six continents; (ii) six circulating CoVs that caused previous human outbreaks of the Common Cold; (iii) five SL-CoVs isolated from bats; (iv) five SL-CoV isolated from pangolins; (v) three SL-CoVs isolated from Civet Cats; and (vi) four MERS strains isolated from camels. Furthermore, we identified cross-reactive asymptomatic epitopes that: (i) recalled B cell, CD4 HGNC+ and CD8 HGNC+ T cell responses from both asymptomatic COVID-19 MESHD patients and healthy individuals who were never exposed to SARS-CoV-2; and (ii) induced strong B cell and T cell responses in humanized Human Leukocyte Antigen (HLA)-DR/ HLA-A HGNC*02:01 double transgenic mice. The findings herein pave the way to develop a pre-emptive multi-epitope pan-Coronavirus vaccine to protect against past, current, and potential future outbreaks.

    SARS-CoV-2 Uses CD4 HGNC to Infect T Helper Lymphocytes

    Authors: Gustavo G. Davanzo; Ana C. Codo; Natalia S. Brunetti; Vinciusi O. Boldrini; Thiago L. Knittel; Lauar B. Monterio; Diogo de Moraes; Allan J. R. Ferrari; Gabriela F. de Souza; Stefanie P. Muraro; Gerson . S Profeta; Natalia S. Wassano; Luana N. Santos; Victor . C Carregari; Arthur . H. S Dias; Joao Victor Virgilio-da-Silva; Icaro Castro; Licia . C Silva-Costa; Andre Palma; Eli Mansour; Raisa G. Ulaf; Ana F. Bernardes; Thyago A. Nunes; Luciana C. Ribeiro; Marcus V. Agrela; Maria Luiza Moretti; Lucas I. Buscaratti; Fernanda Crunfli; Raissa . G Ludwig; Jaqueline A. Gerhardt; Renata Seste-Costa; Julia Forato; Mariene . R Amorin; Daniel A. T. Texeira; Pierina L. Parise; Matheus C. Martini; Karina Bispo-dos-Santos; Camila L. Simeoni; Fabiana Granja; Virginia C. Silvestrini; Eduardo B. de Oliveira; Vitor M. Faca; Murilo Carvalho; Bianca G. Castelucci; Alexandre B. Pereira; Lais D. Coimbra; Patricia B. Rodrigues; Arilson Bernardo S. P. Gomes; Fabricio B. Pereira; Leonilda M. B. Santos; Andrei C. Sposito; Robson F. Carvalho; Andre S. Vieira; Marco A. R. Vinolo; Andre Damasio; Licio A. Velloso; Helder I. Nakaya; Henrique Marques-Souza; Rafael E. Marques; Daniel Martins-de-Souza; Munir S. Skaf; Jose Luiz Proenca-Modena; Pedro M. Moraes-Vieira; Marcelo A. Mori; Alessandro S. Farias

    doi:10.1101/2020.09.25.20200329 Date: 2020-09-28 Source: medRxiv

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as coronavirus disease-2019 ( COVID-19 MESHD). SARS-CoV-2 infects MESHD the lungs and may cause several immune-related complications such as lymphocytopenia MESHD and cytokine storm which are associated with the severity of the disease and predict mortality . The mechanism by which SARS-CoV-2 infection MESHD may result in immune system dysfunction is not fully understood. Here we show that SARS-CoV-2 infects MESHD human CD4 HGNC+ T helper cells, but not CD8 HGNC+ T cells, and is present in blood and bronchoalveolar lavage T MESHD helper cells of severe COVID-19 MESHD patients. We demonstrated that SARS-CoV-2 spike PROTEIN glycoprotein (S PROTEIN) directly binds to the CD4 HGNC molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells in a mechanism that also requires ACE2 HGNC and TMPRSS2 HGNC. Once inside T helper cells, SARS-CoV-2 assembles viral factories, impairs cell function and may cause cell death. SARS-CoV-2 infected MESHD T helper cells express higher amounts of IL-10 HGNC, which is associated with viral persistence and disease severity. Thus, CD4 HGNC-mediated SARS-CoV-2 infection MESHD of T helper cells may explain the poor adaptive immune response of many COVID- 19 patients.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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